Movement of fluorescently labeled molecules (lipids, proteins, carbohydrates) on cell surfaces is observed by fluorescence microscopy, and quantitatively assessed by the technique of fluorescence photobleaching recovery (FPR). Lipids are usually free to move on the cell surface with diffusion constants of about 10-8 cm square/sec. Movement of membrane proteins is often restricted by mechanisms, whose nature is unclear. Two systems were studied in which movement of cell surface components was restricted: 1) In epithelia it appears that the tight junction acts as a barrier to diffusion of certain plasma membrane components between apical and basolateral surfaces: membrane-bound lectins and some lipid probes are incapable of passing through the tight junction region of epithelial membranes. The lectins are immobilized on the cell surface, but the lipid probes diffuse freely in the membrane. The ability of a lipid probe to pass the tight junction is correlated with its ability to "flip-flop" to the inner monolayer of the cell membrane bilayer. 2) In neuroblastoma cells the vast majority of Con A binding sites, which exhibit lateral mobility in undifferentiated cells, become immobilized after induction of differentiation. The mechanism of this immobilization may involve linkage to the internal actin network.